SSRI use and clinical outcomes in epithelial ovarian cancer
SSRI use and clinical outcomes in epithelial ovarian cancer
复制标题
DOI：
10.18632/oncotarget.8891
复制
发表时间：
2016-05-31
期刊：
影响因子：
--
通讯作者：
Lutgendorf, Susan K.
中科院分区：
文献类型：
--
作者：
Christensen, Desire K.;Armaiz-Pena, Guillermo N.;Lutgendorf, Susan K.
选择性血清素再摄取抑制剂（SSRI）的使用在卵巢癌患者中很常见。我们研究了SSRIs对卵巢癌患者生存和进展的影响以及5-HT对卵巢癌细胞（OCC）增殖的影响。1994年至2010年间6个地点的卵巢癌患者被纳入研究。采用Cox比例风险模型进行多变量分析。SSRI使用与疾病复发时间缩短相关（HR 1.3, CI 1.0-1.6, p=0.03），但与总生存期无关（HR 1.1, CI 0.9-1.3, p=0.56）。与正常卵巢细胞相比，大多数OCCs具有升高的5-HT2A受体mRNA表达（高达1600倍的表达）。10 μ m（1.6倍，p< 0.001）和20 μ m(1.9倍，p=0.018) 5-HT处理的细胞克隆存活率增加。注射5-HT的小鼠肿瘤重量增加（p=0.07），结节增加（p=0.08）， Ki67表达增加。注射舍曲林后小鼠平均肿瘤重量增加一倍（p=0.16）。5-HT和舍曲林均能提高小鼠肿瘤中Ki67的表达（p < 0.001）。使用SSRIs的患者出现疾病进展的时间显著缩短。SSRIs可能改变肿瘤微环境中的血清素水平，导致增殖途径的激活。建议进一步表征血清素在卵巢癌中的作用途径，以证明这些药物的安全性。
Selective serotonin reuptake inhibitor (SSRI) use is common among ovarian cancer patients. We examined the effect of SSRIs on survival and progression in ovarian cancer patients and effects of 5-HT on ovarian cancer cell (OCC) proliferation. Ovarian cancer patients from a 6-site study between 1994 and 2010 were included. Cox proportional hazards models were used for multivariate analysis. SSRI use was associated with decreased time to disease recurrence (HR 1.3, CI 1.0-1.6, p=0.03), but not overall survival (HR 1.1, CI 0.9-1.3, p=0.56). Compared to normal ovarian cells, most OCCs had elevated 5-HT2A receptor mRNA expression (up to 1600 fold greater expression). Clonogenic survival increased in cells treated with 10 uM (1.6 fold, p< 0.001) and 20uM (1.9 fold, p=0.018) 5-HT. Mice receiving 5-HT injections had increases in tumor weight (p=0.07) and nodules (p=0.08) with increased Ki67 expression. Injections with sertraline doubled mean tumor weight in mice (p=0.16). 5-HT and sertraline both increased Ki67 expression in mouse tumors (p < 0.001).Patients using SSRIs had significantly decreased time to disease progression. It is possible that SSRIs alter serotonin levels in the tumor microenvironment, resulting in activation of proliferation pathways. Further characterization of serotonergic pathways in ovarian cancer is recommended to demonstrate safety of these medications.